Reitinger Jeremy C, Reed David M, Peres Cameron, Fan Shan, Gulati Vikas, Kazemi Arash, Sit Arthur J, Moroi Sayoko E, Toris Carol B
Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana.
Department of Ophthalmology and Visual Sciences, The Ohio State University, Columbus, Ohio.
J Ocul Pharmacol Ther. 2025 Jun;41(5):251-258. doi: 10.1089/jop.2024.0112. Epub 2025 Apr 14.
To identify reasons for variable intraocular pressure (IOP) responses to latanoprost and timolol in healthy volunteers and to generate the control group as part of Eye Dynamics and Engineering Network. In this multicenter, randomized, crossover study (NCT01677507), both eyes of 106 healthy subjects (212 eyes) were treated with latanoprost or timolol for 7 days, with a 6-week washout between treatments. Ocular biometrics, tonometry, and aqueous humor dynamics (AHD) were assessed at baseline and day 8 of each treatment. Subjects were divided into responders and nonresponders using cutoffs of >15% or >10% IOP reduction. Treatment effects and correlations were analyzed with paired t-tests. More subjects responded to latanoprost (54%) than timolol (27%) at >15% cutoff ( < 0.01). Responders had higher mean baseline IOP than nonresponders for both drugs at both cutoffs ( < 0.01). Among timolol nonresponders ( = 56), 39% responded to latanoprost in both eyes, 20% in one eye, and 41% in neither. Among latanoprost nonresponders ( = 31), 13% responded to timolol in both eyes, 13% in one eye, and 74% in neither. Latanoprost increased uveoscleral outflow, while timolol reduced aqueous flow and outflow facility. Low baseline uveoscleral outflow was associated with latanoprost response. Higher baseline IOP predicted better responses to both drugs. Higher baseline uveoscleral outflow predicted nonresponse to latanoprost. No AHD differences were linked to the timolol response. Timolol nonresponders were often responsive to latanoprost, but not vice versa.
确定健康志愿者对拉坦前列素和噻吗洛尔眼压(IOP)反应各异的原因,并作为眼动力学与工程网络的一部分建立对照组。在这项多中心、随机、交叉研究(NCT01677507)中,106名健康受试者(212只眼)的双眼接受拉坦前列素或噻吗洛尔治疗7天,治疗之间有6周的洗脱期。在每次治疗的基线和第8天评估眼部生物特征、眼压测量和房水动力学(AHD)。使用眼压降低>15%或>10%的临界值将受试者分为反应者和无反应者。采用配对t检验分析治疗效果和相关性。在>15%的临界值时,对拉坦前列素产生反应的受试者(54%)多于噻吗洛尔(27%)(P<0.01)。在两个临界值下,两种药物的反应者的平均基线眼压均高于无反应者(P<0.01)。在噻吗洛尔无反应者(n = 56)中,39%的双眼对拉坦前列素产生反应,20%的单眼产生反应,41%的双眼均无反应。在拉坦前列素无反应者(n = 31)中,13%的双眼对噻吗洛尔产生反应,13%的单眼产生反应,74%的双眼均无反应。拉坦前列素增加了葡萄膜巩膜流出,而噻吗洛尔减少了房水生成和流出易度。低基线葡萄膜巩膜流出与拉坦前列素反应相关。较高的基线眼压预示着对两种药物的反应更好。较高的基线葡萄膜巩膜流出预示着对拉坦前列素无反应。没有AHD差异与噻吗洛尔反应相关。噻吗洛尔无反应者通常对拉坦前列素敏感,但反之则不然。